PROJECT SUMMARY Age-related macular degeneration (AMD) is the number one cause of blindness in adults greater than 60 years of age and the third overall cause of blindness worldwide. Over 2 million adults are affected in the United States and this number is expected to more than double by 2050. Vision loss due to AMD has severe consequences for patients including loss of independence, occupation, and quality of life. AMD is divided into two broad categories: dry AMD and wet AMD. While both can result in loss of vision, it is the wet form that accounts for 90% of AMD associated vision loss. The hallmark of wet AMD is choroidal neovascularization (CNV), which is the growth of abnormal blood vessels from the choroid into the subretinal space. These vessels result in bleeding, swelling, scar tissue formation, and irreversible damage to the eye. Unfortunately, we do not yet fully understand the mechanism behind CNV and scar formation and many patients suffer from severe vision loss as a result. Adenosine is a molecule that is generated at sites of tissue injury and has been shown to play an important role in the development of neovascularization and fibrosis in other parts of the body. Utilizing an established animal model of neovascular AMD, we have generated data demonstrating that adenosine is involved in CNV and fibrosis development. This preliminary data is the first in-vivo evidence implicating adenosine?s involvement in in neovascular AMD. The goal of this proposal is to further explore and dissect the role of adenosine in neovascular AMD in order to discover a novel drug target for this blinding disease. As a clinician-scientist, it is my career goal to bridge basic science and clinical medicine. My graduate school training in adenosine biology and my clinical expertise as a vitreoretinal surgeon serve as a strong foundation to purse my research interests of understanding the molecular pathogenesis behind retinal diseases. The unique research environment at UTHealth with many world-renowned faculty investigating various aspects of adenosine biology will greatly facilitate my academic growth. With the mentoring and career development plan supported by this proposal, I will gain the additional skills and knowledge in retinal biology, immunology, and animal models of macular degeneration required to become an independent investigator with a productive translational basic science research program.